The mariner/Tc1 superfamily of transposable elements is widely distrib
uted in animal genomes and is especially prevalent in insects. Their w
ide distribution results from their ability to be disseminated among h
osts by horizontal transmission and also by their ability to persist i
n genomes through multiple speciation events. Although a great deal is
known about the molecular mechanisms of transposition and excision, v
ery little is known about the mechanisms by which transposition is con
trolled within genomes. The issue of mariner/Tc1 regulation is critica
l in view of the great interest in these elements as vectors for germl
ine transformation of insect pests and vectors of human disease. Sever
al potentially important regulatory mechanisms have been identified in
studies of genetically engineered mariner elements. One mechanism is
overproduction inhibition, in which excessive wild-type transposase re
duces the rate of excision of a target element. A second mechanism is
mediated by certain mutant transposase proteins, which antagonize the
activity of the wild-type transposase. The latter process may help exp
lain why the vast majority of MLEs in nature undergo 'vertical inactiv
ation' by multiple mutations and, eventually, stochastic loss. Another
potential mechanism of regulation may result from transposase titrati
on by defective elements that retain their DNA binding sites and abili
ty to transpose. There is also evidence that some mariner/Tc1 elements
can be mobilized in a type of hybrid dysgenesis.